NM_020890.3:c.686G>T

Variant names:

• chr3-108579413-C-A
• rs2278911
• NM_020890.3:c.686G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020890.3(CIP2A):​c.686G>T​(p.Arg229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CIP2A NM_020890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 34 publications found

Genes affected

CIP2A (HGNC:29302): (cellular inhibitor of PP2A) Enables protein homodimerization activity. Predicted to act upstream of or within positive regulation of neural precursor cell proliferation and spermatogenesis. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIP2A	NM_020890.3	c.686G>T	p.Arg229Leu	missense_variant	Exon 7 of 21	ENST00000295746.13	NP_065941.2
CIP2A	XM_006713716.4	c.683G>T	p.Arg228Leu	missense_variant	Exon 7 of 21		XP_006713779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13	c.686G>T	p.Arg229Leu	missense_variant	Exon 7 of 21	1	NM_020890.3	ENSP00000295746.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455500 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724214

African (AFR) AF: 0.00 AC: 0 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.00 AC: 0 AN: 85336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107596

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	0.0069	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.8	L;.;.
PhyloP100		2.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.2	D;D;.
REVEL	Benign	0.093
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.30	B;.;.
Vest4		0.62
MutPred		0.47		Gain of helix (P = 0.0696);.;Gain of helix (P = 0.0696);
MVP		0.60
MPC		0.41
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.67
gMVP		0.30
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2278911; hg19: chr3-108298260;